ArticleOncotarget2015
Stromal-derived factor-1α/CXCL12-CXCR4 chemotactic pathway promotes perineural invasion in pancreatic cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 78 citations in OpenAlex.
- Neuroimmune crosstalk in cancer: emerging immunotherapeutic opportunities.Journal for immunotherapy of cancer · 2026Review
- Integrins as key regulators in tumor perineural invasion: mechanisms and clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Decoding Pancreatic Cancer Pain: From Tumor-Nerve Crosstalk to Targeted Analgesic Strategies.International journal of medical sciences · 2026Review
- CCR-CCL axes as key upstream influencers of pancreatic ductal adenocarcinoma: CCR2-CCL2, CCR5-CCL5, CCR4-CCL17/22, CCR6-CCL20, CCR7-CCL19/21.Frontiers in immunology · 2026Review
- The neural niche in cancer: mechanistic insights into tumor-neuron-immune crosstalk and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Peripheral nerve remodeling in the tumor microenvironment: neuro-immune crosstalk, molecular mechanisms, and precision therapeutic.Frontiers in immunology · 2026Review
- Perineural Invasion in Pancreatic Ductal Adenocarcinoma: Recapitulating Its Importance and Defining Future Directions.United European gastroenterology journal · 2025Review
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Cancer-nervous system crosstalk: from biological mechanism to therapeutic opportunities.Molecular cancer · 2025Review
- Targeting Perineural Invasion in Pancreatic Cancer.Cancers · 2024Review
- Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- The Role of Chemokines in Orchestrating the Immune Response to Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- NGF-mediated crosstalk: unraveling the influence of metabolic deregulation on the interplay between neural and pancreatic cancer cells and its impact on patient outcomes.Frontiers in pharmacology · 2024Review
- Investigation of the correlation between AGRN expression and perineural invasion in colon cancer.Frontiers in molecular biosciences · 2024Article
- Hallmarks of perineural invasion in pancreatic ductal adenocarcinoma: new biological dimensions.Frontiers in oncology · 2024Review
- Periampullary cancer and neurological interactions: current understanding and future research directions.Frontiers in oncology · 2024Review
- Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.Neuroscience bulletin · 2023Review
- Targeting the Cancer-Neuronal Crosstalk in the Pancreatic Cancer Microenvironment.International journal of molecular sciences · 2023Review
- Genetic Mouse Models to Study Pancreatic Cancer-Induced Pain and Reduction in Well-Being.Cells · 2022Article
- Nanoemulsion-Assisted siRNA Delivery to Modulate the Nervous Tumor Microenvironment in the Treatment of Pancreatic Cancer.ACS applied materials & interfaces · 2022Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perineural invasion (PNI) is considered as an alternative route for the metastatic spread of pancreatic cancer cells; however, the molecular changes leading to PNI are still poorly understood. In this study, we show that the CXCL12/CXCR4 axis plays a pivotal role in the neurotropism of pancreatic cancer cells to local peripheral nerves. Immunohistochemical staining results revealed that CXCR4 elevation correlated with PNI in 78 pancreatic cancer samples. Both in vitro and in vivo PNI models were applied to investigate the function of the CXCL12/CXCR4 signaling in PNI progression and pathogenesis. The results showed that the activation of the CXCL12/CXCR4 axis significantly increased pancreatic cancer cells invasion and promoted the outgrowth of the dorsal root ganglia. CXCL12 derived from the peripheral nerves stimulated the invasion and chemotactic migration of CXCR4-positive cancer cells in a paracrine manner, eventually leading to PNI. In vivo analyses revealed that the abrogation of the activated signaling inhibited tumor growth and invasion of the sciatic nerve toward the spinal cord. These data indicate that the CXCL12/CXCR4 axis may be a novel therapeutic target to prevent the perineural dissemination of pancreatic cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.